Omar P. Sangueza

Intravascular and diffuse dermal reactive angioendotheliomatosis secondary to iatrogenic arteriovenous fistulas.

Reactive angioendotheliomatosis is a rare benign process that has been mainly described in patients with systemic infections, such as subacute bacterial endocarditis or tuberculosis, and in association with intravascular deposition of cryoproteins. Histopathologically, it is characterized by a proliferation of endothelial cells within vascular lumina resulting in the obliteration of the involved vessels. Another rare variant of reactive angioendotheliomatosis has been described in the lower extremities of patients with severe peripheral vascular atherosclerotic disease. It consists of violaceous and purpuric plaques histopathologically characterized by diffuse prolifrration of endothelial cells interstitially arranged between collagen bundles of the reticular dermis. This second variant has been named diffuse dermal reactive angioendotheliomatosis. We report two patients with reactive cutaneous angioendotheliomatosis appearing distally to arteriovenous fistulas used for hemodialysis because of chronic renal failure. The first patient showed intravascular reactive angioendotheliomatosis, while the second one had purpuric plaques that were characterized histopathologically by diffuse dermal angioendotheliomatosis. Both patients showed an arteriovenous “steal” syndrome with distal ischemia, and it is possible that a local increase of vascular endothelial growth factor, as is the case in hypoxia situations, induces the endothelial proliferation. To the best of our knowledge, cutaneous reactive angioendotheliomatosis has not been previously described in association with arteriovenous shunts.

Immunohistochemical evaluation of basal cell carcinoma and trichepithelioma using Bcl‐2, Ki67, PCNA and P53

Most basal cell neoplasms with follicular differentiation represent a heterogenous group of tumors. Although may arise anywhere in the skin, these neoplasms commonly occur on the head and neck regions. The majority of these neoplasms are basal cell carcinomas (BCC) and trichoepitheliomas (TE). Overlapping histopathologic features between these benign and malignant tumors are occasionally seen which may create problems in rendering a definitive diagnosis. The intent of this investigation was two‐fold: 1) to examine whether there are quantitative differences of the cellular expression of Bcl‐2, Ki67, PCNA and P53 between BCC and TE; and 2) to examine the value of these immunostains in differentiating between BCC and TE. Twenty cases of BCC were stained with antibodies for Bcl‐2, Ki67, PCNA and P53. The positive cell indices and staining characteristic of these immunostains were compared with those of 20 cases of TE. The cell indices for each group were analyzed statistically utilizing the analysis of variance (ANOVA) technique. Intensity and patterns of Bcl‐2 and P53 expression were similar between BCC and TE. The ANOVA analysis showed no statistically significant differences between cell indices for cases stained with antibodies for Bcl‐2 and P53 (p=0.49 and p=0.87 respectively) in the two neoplastic groups. There were intense labelling and generalized patterns of Ki67 and PCNA expression in BCC. Conversly, Ki67‐ and PCNA‐labelled cells were much fewer in TEs than those noted in BCCs. Additionally, Ki67‐ and PCNA‐positive cells were limited to the peripheral layers of the neoplastic islands of TEs. There were statistically significant differences between cell indices for cases stained with antibodies for Ki67 and PCNA (p=0.02 and p=0.05 respectively) in the two neoplastic groups. BCC and TE exhibited comparable expressions of Bcl‐2 and P53 with similar intensity of labelling and patterns of distribution. This suggests possible similar mechanisms of growth regulation in both neoplasms. However, Ki67 and PCNA labelling was noted with significantly increased numbers and recognizably different patterns in BCCs compared to TEs. This may help explain the significant capabilities in tumor proliferation and the aggressive behavior of BCC compared to the limited growth potential of TE. Additionally, Ki67 and PCNA staining intensity and charactristics may have some value in differentiating between BCC and TE.

Clear-cell atypical fibroxanthoma: an uncommon histopathologic variant of atypical fibroxanthoma

Atypical fibroxanthoma is a superficial variant of pleomorphic malignant fibrous histiocytoma. Histopathologically, it is characterized by a dermal nodule composed of bizarre cells arranged in a haphazard‐to‐fascicular pattern. These cells are spindle or rounded, pleomorphic and with numerous atypical mitotic figures. Some cells appear polygonal with ample and foamy cytoplasm. We recently encountered two elderly patients with atypical fibroxanthoma on their face. Histopathologically, one of the lesions was composed, almost entirely, of clear cells, whereas in the other one aggregations of clear cells constituted a half of the neoplasm. Atypical multinucleated cells with a Touton‐like appearance were present. In addition to clear cells, areas of more conventional atypical spindle cells arranged in fascicles were seen, supporting the diagnosis of atypical fibroxanthoma. PAS staining failed to demonstrate glycogen in neoplastic cells. Immunohistochemistry revealed that neoplastic cells expressed positivity for vimentin, muscle‐specific actin, and alpha smooth muscle actin, whereas cytokeratin, S‐100 protein, EMA, CEA, and clesmin were negative. Ultrastructural studies showed that neoplastic cells contained abundant rough endoplasmic reticulum, mitochondria, and numerous lipid vacuoles within the cytoplasm. Clear‐cell atypical fibroxanthoma is a rare variant of atypical fibroxanthoma that should be differentiated from other clear‐cell neoplasms of the skin.

Juvenile xanthogranuloma: A clinical, histopathologic and immunohistochemical study

Juvenile xanthogranuloma (JXC) is a benign histiocylic proliferation of uncertain histogenesis which usually resolves spontaneously. Histopathologically, classic lesions are characterized by diffuse proliferations of foamy histiocytes, many of which may be multinucleated (Toulon cells), admixed with lymphocytes and eosinophils. Histologic variants of JXG, perhaps representing evolving lesions, may lack these typical histopathological features, showing diffuse infiltrates of non‐foamy mononuclear histiocytes without Toulon cells, posing problems in differentiation from other histiocylic or melanocylic proliferations. Immunohistochemically, JXG is characterized by variable expressions of several histiocytic markers as well as the absence of staining for SI00 protein. To assess better the spectrum of histopathological and immunohistochemical features of JXG, we studied nine cases of classic or histologic variant of JXG. The cases were evaluated by light microscopy and with an extensive battery of antibodies. All 9 cases, regardless of their light microscopic appearance, showed markedly positive staining with histiocytic markers including CD68, HAM56, cathepsin B and vimentin, but did not stain for S100 protein. Antibodies to factor XIIIa stained positively in 8 cases while staining for other markers was variable. Our results suggest that the histiocytes in JXG lesions have macrophagic differentiation, probably representing a reactive process to an unknown stimulus.

Treatment of scleromyxedema with 2-chlorodeoxyadenosine

Scleromyxedema is an unusual skin disease that is characterized by a proliferation of fibroblasts and an accumulation of mucin. Despite experience with multiple forms of therapy, no single agent has proved uniformly beneficial in this condition. We describe a patient with scleromyxedema who was treated successfully with 2-chlorodeoxyadenosine (2-CdA), a purine analog used mainly in the treatment of lymphoproliferative disorders.

Familial cutaneous collagenoma

Address for correspondence: Marianne E. Dawn, MD, Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, 6th Floor, Baltimore, MD 21201 E-mail: marianne.dawn@gmail.com A 41-year-old woman presented to our dermatology clinic in February 2005 with a chief complaint of numerous fleshcolored nodules on her back and abdomen. She initially noticed the lesions at age 17 years. The plaques had increased in size and number over time, but remained asymptomatic. The patient reported multiple similar lesions on a maternal uncle and a cousin. Her family history was also notable for cardiomyopathy, resulting in the death of her mother. The patient’s past medical history was notable for poorly controlled type I diabetes, currently managed with an insulin pump; and coronary artery disease. The patient had undergone multiple cardiac procedures before the age of 40 years, including quadruple coronary artery bypass grafting surgery and placement of 9 cardiac stents. Her ejection fraction on cardiac catheterization in November 2004 was 65% with no wall motion abnormalities. On physical examination, numerous spongy, discrete, flesh-colored plaques and nodules were seen concentrated across the upper part of her back between the scapulae as well as underneath the breasts and across the flanks (Figure 1). All lesions were asymptomatic. Prior workup of this patient had included plain films of the long bones and hands, which were within normal limits. A biopsy from lesional skin on the back highlighted by trichome stain showed an increased number of markedly thickened and eosinophilic dermal collagen bundles compared with adjacent normal skin. Immunohistochemical studies with anticollagen type I and type III antibodies confirmed that the increased collagen material consisted of type I collagen fibers, which is the same type of collagen found in normal dermis. The elastic fibers, highlighted by Verhoeff-van Gieson stain (Figure 2), were diminished and haphazardly arranged. No increased cellular component or inflammatory infiltrate was observed. These findings were consistent with a collagenoma. Further analysis of the lesional tissue by electron microscopy revealed that the ultrastructural appearance of the collagen fibers, including arrangement and diameters, were not significantly different from that of the normal tissue (Figure 3).

Adenosquamous carcinoma: A case report with immunohistochemical evaluation

The histogenetic origin of adenosquamous carcinoma, a high-grade variant of malignant epithelial neoplasm, has long been debated. We report a case that clearly demonstrated a mucosal surface epithelial origin. This concept was supported through histologic analysis of hematoxylin- and eosin-stained sections, as well as by the pattern of immunohistochemical reactivity with antibodies directed against low and high molecular weight cytokeratins, cell adhesion molecules (CAM 5.2), and carcinoembryonic antigens. The histologic differential diagnosis, biological behavior, and prognosis of adenosquamous carcinoma are also examined.

Metastatic Crohn's disease

Metastatic Crohns disease is the term used for granulomatous lesions of Crohns disease involving sites other than the gastrointestinal tract. Metastatic Crohns disease has been considered uncommon, when in actuality it may simply be underdiagnosed or misdiagnosed since the clinical findings can be different. We report on three patients with this condition: one with generalized plaques, another with perineal and perianal ulcerations, and a third with a painless forearm nodule.

Absence of Epstein-Barr virus in lymphomatoid papulosis: An immunohistochemical and in situ hybridization study

BACKGROUND AND DESIGN Lymphomatoid papulosis (LyP) and cutaneous Hodgkins disease share many clinical, histopathologic, and immunohistochemical features. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of several lymphoid malignancies, including Hodgkins disease. Given the similarities between LyP and Hodgkins disease, we asked if EBV could be detected in lesions of LyP. We examined 31 specimens of LyP that were obtained from 24 patients for evidence of EBV by in situ hybridization to EBER1 transcripts and for immunohistochemistry of viral latent membrane protein 1 (LMP1). RESULTS In no instance there was there any evidence of EBV gene products by either in situ hybridization or immunohistochemistry. CONCLUSIONS The absence of EBV in LyP suggests that this virus is not operative in the pathogenesis of LyP. Furthermore, it suggests that LyP and Hodgkins disease may not share the same molecular mechanisms despite their phenotypic similarities.

Axillary granular parakeratosis

A healthy 62‐year‐old African–American woman had noted an intermittent eruption in both axillae for 5 years. She had been using a well‐known, brand name, roll‐on deodorant–antiperspirant 1 month prior to the start of her eruption. She continued to use the same product intermittently for years despite this eruption, and noticed improvement after stopping it for a short period of time. She denied any erythema, pruritus, or foul odor and denied any relation to clothing or environmental temperature. The patient had tried no other treatment for her eruption prior to her clinic visit. The lesions consisted of well‐demarcated, linear, hyperpigmented, brown, thin, vegetative plaques in her axillae, which peeled off with gentle manipulation ( Figs 1 and 2 ).